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Biomedical subjects

M Gambacciani

Publications and source records attributed to M Gambacciani.

At least 55 records · Page 3Linked to original sources
PubMed1997

Bone density changes in postmenopausal women with the administration of ipriflavone alone or in association with low-dose ERT.

Ipriflavone is a synthetic flavonoid that has been shown to exert a direct inhibitory effect on osteoclastic activity and possibly stimulate the osteoblast activity in different experimental models. The aim of the present study was to evaluate the effects of either ipriflavone alone or ipriflavone plus low dose hormone replacement therapy (HRT) in the prevention of postmenopausal bone loss. Patients were randomly allocated to different treatment groups receiving calcium (500 mg/day, control group), continuous HRT (25 or 50 micrograms/day of transdermal 17 beta-estradiol) plus medrogestone 5 mg/day for 12 days/month, ipriflavone at the standard dose of 600 mg/day, or finally ipriflavone 600 mg/day plus 17 beta-estradiol 25 micrograms/day plus medrogestone 5 mg/day for 12 days/month. No significant differences in basal levels of biochemical markers of bone turnover or in basal bone mineral density (BMD) values were evident in the different groups. In the control group after 12 months, spine BMD showed a significant (p < 0.05) 3.41% decrease. The pattern of BMD modification was significantly different from controls in the high dose HRT group (+1.84%), the ipriflavone group (+0.11%), and the combined ipriflavone/HRT group (-0.22%). Conversely, the BMD pattern in the low dose HRT group (-0.55%) was similar to that observed in controls. Thus, present results confirm that ipriflavone and 50 micrograms/day of transdermal 17 beta-estradiol are effective measures in the prevention of postmenopausal osteopenia. A lower transdermal estrogen dose is unable to increase the antiresorptive effect of ipriflavone and did not exert any further action in the prevention of postmenopausal osteopenia.

Administration, Cutaneous↗
PubMed1995

Treatment of postmenopausal vertebral osteopenia with monofluorophospate: a long-term calcium-controlled study.

The aim of the present study was to assess the effects of the new fluorine pro-drug monofluorophosphate (MFP) in postmenopausal women with vertebral osteopenia and high bone turnover. We enrolled postmenopausal women (PMW, 43-59 years) who had had a natural menopause 2-5 years before the study, had vertebral bone mineral density (BMD) < 1 SD from the premenopausal mean, and had at least one of the biochemical markers of bone remodeling > 1 SD over the mean for premenopausal women. Patients were randomly divided into two treatment groups (group 1, 500 mg/day of oral calcium; group 2, MFP at the dose of 20 mg F-equivalents + 600 mg calcium/day) for 2 years (n = 21 in each group). The lumbar vertebral (L2-4) BMD and total body bone mineral (TBBM) were measured by dual-energy X-ray absorptiometry (Lunar DPX, Lunar Corporation, USA). Urinary hydroxyproline excretion (OH-P/Cr), plasma bone Gla protein (BGP) and serum alkaline phosphatase (AP) were assayed. In group 1 the markers of bone turnover and vertebral BMD did not show any significant modification, while TBBM showed a significant (p < 0.05) decrease after 24 months. In group 2 a significant (p < 0.05) decrease in OH-P/Cr (-23.9 +/- 2.0%), and an increase in both BGP (+19.4 +/- 2.6%) and AP (+10.3 +/- 2.6%) levels were observed after 24 months of MFP administration. In this group, both vertebral BMD (+5.01 +/- 0.9%, p < 0.01) and TBBM (+4.0 +/- 0.6%, p < 0.05) showed a significant increase after 24 months. Present results suggest that, in osteopenic PMW, MFP administration induces a significant increase in vertebral BMD without impairment of cortical bone, with a reduction in bone resorption and an increase in bone formation rate.

Adult↗
PubMed1995

Ultrasonographic bone characteristics during normal pregnancy: longitudinal and cross-sectional evaluation.

OBJECTIVE: We evaluated the pattern of bone density during pregnancy by radiation-free ultrasonographic densitometry. STUDY DESIGN: In a longitudinal study we measured bone mineral density in a group of 10 normal primiparous women, from the fourteenth to the thirty-eighth weeks of pregnancy. In a cross-sectional study bone mineral density was determined in a group of 85 normal primiparous women, in different weeks of pregnancy. RESULTS: In the longitudinal study ultrasonographic bone density was stable in the first part of pregnancy, whereas a significant (p < 0.05) decrease was evidenced during the third trimester. A negative correlation between bone density and weeks of pregnancy (p < 0.0001) was evidenced in the cross-sectional study. CONCLUSION: During physiologic pregnancy the calcium mobilization from the maternal bone stores to accomplish the fetal needs can cause a significant decrease in maternal bone density in the last trimester of gestation.

Bone Density↗
PubMed1995

Effects of a new estrogen/progestin combination in the treatment of postmenopausal syndrome.

Postmenopausal women were randomly given either oral calcium (500 mg/day, control group, n = 12) or a combination of estradiol valerate (EV, 2 mg/day for 21 days) with cyproterone acetate (CPA, 1 mg/day in the last 10 days of the treatment cycle, n = 19). EV+CPA reduced (P < 0.01) postmenopausal complaints, inducing regular withdrawal bleeds, with no hysteroscopic or hystologic evidence of endometrial hyperstimulation after 12 months of treatment. In the control group, spine bone mineral density (BMD) and the total body bone mineral (TBBM) decreased (P < 0.01), whereas urinary hydroxyproline excretion (OH-P/Cr), plasma bone Gla Protein (BGP) and lipid profile did not show any significant modification throughout the study. In the EV+CPA group, urinary OHP/Cr and plasma BGP levels decreased (P < 0.01) after 6 and 12 months, whereas both BMD and TBBM showed a small but significant (P < 0.01) increase. In this group, LDL cholesterol significantly (P < 0.01) decreased and HDL levels significantly (P < 0.01) increased after 6 and 12 months. In conclusion, the EV+CPA combination is effective in relieving menopausal symptoms, produces a good cycle control and a favourable lipid profile, preventing postmenopausal bone resorption.

Adult↗
PubMed1995

Prospective evaluation of calcium and estrogen administration on bone mass and metabolism after ovariectomy.

We evaluated the effects of low-dose ethinylestradiol administration in the prevention of the rapid bone loss that follows ovariectomy in women. After 10-30 days from surgery, patients received either a sole calcium supplementation 500 mg/day (n = 20) or ethinylestradiol 20 micrograms/day in addition to the same daily calcium supplement (n = 21), for 12 months. In the control group, urinary hydroxyproline excretion, serum alkaline phosphatase and plasma bone Gla protein levels presented a substantial (p < 0.05) increase, while radial bone density significantly (p < 0.05) decreased 6 months after surgery. In the ethinylestradiol-treated group, the patterns of biochemical markers indicated that ethinylestradiol can restrain the bone remodelling processes. Radial bone density showed no significant modification during the 12 months' study period. In conclusions, these results demonstrate that the administration of 20 micrograms/day of ethinylestradiol can prevent the rapid bone loss that follows ovariectomy.

Administration, Oral↗
PubMed1994

Hormone replacement therapy in perimenopausal women with a low dose oral contraceptive preparation: effects on bone mineral density and metabolism.

In a 2-year longitudinal, calcium-controlled study we evaluated bone density and metabolism in perimenopausal women with initial ovarian failure, and the effects of hormone replacement with a low dose oral contraceptive preparation (OC). In perimenopausal oligomenorrhoic women (n = 16) a significant (P < 0.01) increase in cycle length and plasma FSH levels as well as a parallel decrease in plasma estradiol levels (P < 0.01) were evident. In this group, despite the calcium supplementation (500 mg/day), a significant (P < 0.001) increase in the biochemical markers of bone remodelling paralleled a significant (P < 0.001) decrease (-3.4% after 24 months) in bone density. Conversely, in premenopausal oligomenorrhoic women treated with a low dose oral contraceptive (OC) formulation (30 mcg ethinyl estradiol plus 75 mcg gestodene, n = 16), bone markers showed a significant (P < 0.01) decrease, that paralleled a slight but significant (P < 0.01) increase (+1.71%) in bone density. These data suggest that premenopausal administration of OC can prevent the acceleration of bone turnover and reverse the decrease in bone density that follows the premenopausal impairment of ovarian function.

Administration, Oral↗
PubMed1994

Bone loss in perimenopausal women: a longitudinal study.

A longitudinal evaluation of bone mineral density (BMD) and metabolism was performed in premenopausal women. During the 2-year observation period, the menstrual pattern, plasma estradiol and FSH levels as well as the values of bone markers and BMD did not show any significant modification in a group of eumenorrhoic women (n = 37). Conversely, in age-matched oligomenorrhoic women (n = 37) a significant (P < 0.05) increase in the cycle length with a concomitant significant (P < 0.05) increase in circulating plasma FSH and parallel decrease of plasma estradiol levels (P < 0.05) was evident. In this group a significant (P < 0.05) increase in both urinary excretion of OH-P/Cr and plasma BGP levels paralleled a significant (P < 0.05) decrease in radial BMD. These data suggest that premenopausal impairment of ovarian function can lead to a bone loss in a significant proportion of women in which prevention should be considered before menopause.

Adult↗
PubMed1994

Ipriflavone prevents the bone mass reduction in premenopausal women treated with gonadotropin hormone-releasing hormone agonists.

In the present study we assessed the effects of ipriflavone in the prevention of increased bone turnover and the rapid bone loss that follows medical induced hypogonadism caused by the administration of a gonadotropin hormone-releasing hormone agonist (GnRH-A). In a double blind, placebo-controlled study, ipriflavone (600 mg/day, tdd (three divided doses)) or identical placebo tablets were given with 500 mg/day of calcium to patients treated with 3.75 mg leuproreline acetate every 30 days, for 6 months. In placebo-treated subjects (n = 39), urinary hydroxyproline excretion and plasma bone GLA protein levels showed a substantial (P < 0.01) increase, while spine bone density and total body bone density significantly (P < 0.01) decreased after 3 and 6 months of GnRH-A administration. Conversely, in ipriflavone treated group (n = 39), no significant difference in bone markers and bone density was evidenced. These data indicate that ipriflavone can restrain the bone remodeling processes and prevent the rapid bone loss that follows medical induced hypogonadism. Thus, ipriflavone administration can be of value in the prevention of osteopenia in women treated with GnRH-A.

Adult↗
PubMed1994

Autonomous gonadotropin release from the human pituitary in vitro and factors influencing this secretion.

Our understanding of the hypothalamus as the sole pacemaker for episodic hormone release has been challenged by recent observations of an autonomous rhythmic secretion from the pituitary, independent of hypothalamic inputs. Using an in vitro perifusion system, we were able to demonstrate an intrinsically pulsatile gonadotropin secretion from human fetal and adult pituitaries. This high-frequency/low-amplitude release is calcium-dependent and stimulated by gonadotropin releasing hormone (GnRH) administrations. Also, the autonomous release of luteinizing hormone (LH) appears to be temporally and functionally linked to the spontaneously pulsatile secretion of other anterior pituitary hormones, suggesting the existence of a common intrapituitary mechanism entraining these hormone pulsatilities. Further, the spontaneous and GnRH-stimulated LH release is greater from human female fetal pituitaries than from male fetal pituitaries at mid-gestation, presumably a reflection of differences in the negative feedback actions by factors from the fetal gonads. Collectively, we have observed an autonomous gonadotropin release from the human pituitary independent of, but facilitated by, GnRH. This spontaneous pulsatile secretion is calcium-dependent and entrained to the release of other anterior pituitary hormones. Therefore, it may represent the activity of a common intrapituitary pulse-generating mechanism and its modulation by factors from inside and outside the human pituitary.

Calcium↗
PubMed1994

Longitudinal evaluation of perimenopausal vertebral bone loss: effects of a low-dose oral contraceptive preparation on bone mineral density and metabolism.

OBJECTIVE: To characterize the pattern of biochemical markers of bone metabolism and vertebral bone mineral density in eumenorrheic and oligomenorrheic perimenopausal women and to assess the effects of a combined oral contraceptive (OC) preparation on bone mass and metabolism. METHODS: Bone biochemical markers and vertebral bone density were evaluated in a longitudinal 2-year follow-up study conducted in healthy, normally menstruating perimenopausal women, perimenopausal oligomenorrheic women, and age-matched oligomenorrheic OC-treated women (20 micrograms ethinyl estradiol [E2] plus 0.15 mg desogestrel) (n = 27 in each group). The results were analyzed by factorial or repeated-measures analysis of variance, as appropriate. RESULTS: During our observation period, there were no significant modifications in menstrual cycle, plasma FSH and E2 levels, biochemical markers of bone turnover, and vertebral bone density in normal women. Conversely, oligomenorrheic women showed an increase in the cycle length with a concomitant decrease of plasma E2 and a corresponding rise in circulating plasma FSH levels (P < .05). In this group, an increase in both urinary excretion of hydroxyproline and plasma osteocalcin levels paralleled a significant decrease in vertebral bone density (P < .0001). In OC-treated women, the pattern of osteocalcin showed no modification, whereas urinary excretion of hydroxyproline showed a decrease, which paralleled a significant (P < .001) increase in vertebral bone density. CONCLUSION: Perimenopausal OC administration can prevent the increase in bone turnover and the decrease in bone density that follow the perimenopausal impairment of ovarian function.

Adult↗
PubMed1993

Effects of ipriflavone administration on bone mass and metabolism in ovariectomized women.

The aim of the present study was to assess the effects of ipriflavone administration in the prevention of the rapid bone loss that follows ovariectomy in women. After 10-30 days from bilateral ovariectomy, patients received either the sole calcium supplementation (500 mg/day, n = 16) or ipriflavone (600 mg/day, n = 16) in addition to the same daily calcium supplement for 12 months. In calcium-treated subjects urinary hydroxyproline excretion, serum alkaline phosphatase and plasma bone Gla protein levels showed a substantial (p < 0.01) increase, while radial bone density significantly (p < 0.01) decreased 6 months after surgery. In ipriflavone treated group the patterns of biochemical markers indicated that ipriflavone can restrain the bone remodeling processes and radial bone density showed no significant modification during the 12 month study period. These results demonstrate that ipriflavone administration prevents the rapid bone loss that follows ovariectomy. Thus, ipriflavone can represent an attractive alternative for the prevention of osteoporosis in postmenopausal women who present contraindications to the estrogen replacement therapy.

Bone Density↗
PubMed1993

The relative contributions of menopause and aging to postmenopausal vertebral osteopenia.

Lumbar spine bone mineral density (BMD) was measured by dual energy x-ray absorptiometry in 2190 normal postmenopausal women (PMW). BMD was loosely correlated (r = 0.15) with height, but stronger positive relations were found with body mass index (BMI; r = 0.25) and body weight (r = 0.31). BMD decreased with age (r = 0.25), but the relation with years since menopause (YSM) was the most potent (r = 0.36). BMD shows a rapid and highly significant (P < 0.0001) decrease in the first 5 YSM, when no relation between BMD and age is present. As the menopausal bone loss is not linear, the BMD values were regressed on the logarithmic transformation of YSM, and the equation was y = -0.183 logYSM + 1.149 (r = 0.44; P < 0.0001). When lumbar BMD was simultaneously regressed on different variables, the correlation with BMI and logYSM remained highly significant, whereas the correlation with age was not significant. The age-related component accounts for a linear 0.4% decrease/yr, starting at the age of 55 yr. In 139 pairs of PMW up to and over 60 yr of age (58 +/- 1.9 and 62.5 +/- 1.5 yr, respectively), matched for YSM (10.3 +/- 2.3), no significant differences in height, weight, or BMI were found. The BMD was significantly (P < 0.001) lower in the younger (0.945 +/- 0.13 g/cm2) than in older PMW (1.006 +/- 0.18 g/cm2) despite their identical YSM. In conclusion, the menopausal (hormonal) component of bone loss and a younger at the menopause represent the major factors in determining involutional vertebral osteopenia in women.

Aging↗
PubMed1992

Lack of any estrogenic effect of ipriflavone in postmenopausal women.

Estrogen replacement therapy (ERT) has been demonstrated to prevent osteoporosis in postmenopausal women (PMW). However, several contraindications exist for ERT and many PMW cannot be treated. It has also been shown that too low doses of ERT are able to exert therapeutical effects on some climacteric symptoms but not on bone and compounds exerting synergic actions with ERT on bone without effects on other organs could be useful. The isoflavone derivative, ipriflavone, seems to have this effect but data are lacking on its endocrine effect in humans; thus, this study was undertaken to clarify in PMW whether ipriflavone exerts estrogenic activity. Evaluation of LH and FSH secretion during a 24-h period was performed in a group of 15 PMW after a single oral dose of 600 or 1,000 mg of ipriflavone or placebo, and after 7, 14 and 21 days of oral treatment with ipriflavone 600 mg and 1,000 mg/daily, administered in three divided doses. LH secretion was also evaluated during naloxone infusion before and after 21 days of ipriflavone, placebo or conjugated estrogen treatment (0.625 mg/day; CE). LH response to NAL treatment was absent during ipriflavone and placebo such as it was observed before treatments. By contrast, a significant increase of LH plasma levels was measured during naloxone infusion in CE-treated women. This result demonstrates that ipriflavone is unable to exert the same effects that estrogens do in PMW. In addition, no changes like in placebo group were seen on vaginal cytology in this group of subjects after 21 days, whereas a significant increase of superficial vaginal cells was observed after 21 days of CE treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Estradiol↗
PubMed1992

Ipriflavone and low doses of estrogens in the prevention of bone mineral loss in climacterium.

Estrogen replacement therapy can counteract all postmenopausal symptoms. While low estrogen doses (0.15-0.30 mg of conjugated estrogens/day) can counteract neurovegetative and psychological symptoms, higher estrogen doses (at least 0.625 mg of conjugated estrogens/day) are required to prevent bone mineral loss in postmenopausal women. However, if contra-indications to high estrogen doses exist, drugs other than estrogens can represent a suitable treatment for postmenopausal osteoporosis both alone or in combination with low estrogen doses. Experimental and clinical data have shown that ipriflavone is effective in the treatment of established postmenopausal osteoporosis. With the purpose of evaluating whether ipriflavone is able to enhance estrogen activity on bone metabolism, 133 postmenopausal women were randomly submitted to the treatment with: (1) placebo; (2) 0.15 mg/day of conjugated estrogens; (3) 0.30 mg/day of conjugated estrogens; (4) 0.15 mg/day of conjugated estrogens plus 600 mg/day of ipriflavone; (5) 0.30 mg/day of conjugated estrogens plus 600 mg/day of ipriflavone. One g/day of calcium supplementation was given to all women. In all subjects bone mineral density was measured before and after 6 and 12 months of treatment at the distal radius by dual-photon absorptiometry. A moderate decrease of bone mineral density was evidenced in women submitted to placebo or to estrogen therapy alone. By contrast, an increase of BMD was measured after 12 months of treatment in the women treated with 0.15 (not significant) or 0.30 mg/day (P < 0.01) of conjugated estrogens associated with ipriflavone. Both dosages of conjugated estrogens were able to induce a significant reduction of neurovegetative symptoms. The increase of bone density obtained with the combination of conjugated estrogens with ipriflavone demonstrates that this combination improves the effects of low estrogen doses on bone mass representing a satisfactory approach in the prevention and treatment of all symptoms related to the climacteric syndrome.

Absorptiometry, Photon↗
PubMed1992

Effects of continuous and cyclic nasal calcitonin administration in ovariectomized women.

The aim of the present study was to assess the effects of continuous and cyclic salmon calcitonin (sCT) administration in the prevention of the rapid bone loss that follows ovariectomy in humans. Patients who had undergone bilateral ovariectomy 10-30 days previously received either calcium supplementation alone (500 mg/day, n = 12) or such supplementation together with nasal sCT (200 IU/day) according to a continuous (n = 20) or a cyclic (3 months on, 1 month off) regimen (n = 16) for 2 years. In the calcium-only-treated subjects urinary hydroxyproline excretion, serum alkaline phosphatase and plasma bone Gla protein levels showed a substantial increase (P < 0.01) 6 months after surgery, while radial bone density was found to have decreased significantly (P < 0.01). The patterns of biochemical markers in the sCT-treated groups indicated that nasal sCT can positively uncouple the two bone remodelling processes without inducing any significant change in radial bone density over a 2-year period. No differences were observed between the two sCT-treated groups. These results demonstrate that the rapid bone loss that follows ovariectomy can be prevented by either cyclic or continuous nasal sCT administration. Thus, cyclic nasal sCT represents an attractive alternative for the prevention of osteoporosis in postmenopausal women with contraindications to oestrogen replacement therapy.

Administration, Intranasal↗
PubMed1991

Neuroendocrine and clinical effects of transdermal 17 beta-estradiol in postmenopausal women.

The neuroendocrine and clinical effects of transdermal 17 beta-estradiol (rated at 50 micrograms/day; TTS 50) were studied in 40 postmenopausal women; ten additional postmenopausal women did not receive any drugs. The changes in LH and rectal temperature induced by the infusion of the opioid antagonist naloxone (10 mg i.v. bolus plus 10 mg/h for 4 h) were used to evaluate the central activity of endogenous opioid peptides. TTS 50 increased opioid activity, as evidenced by the restoration of the LH response (P less than 0.01) and the enhancement of the hypothermic effect (P less than 0.05) of naloxone. A greater reduction in hot flushes was observed in TTS 50-treated subjects than in untreated women, with the maximal effect of TTS 50 achieved after 3 months of therapy. TTS 50 did not modify the concentrations of circulating lipids, glucose or liver enzymes but reduced the biochemical parameters indicative of bone reabsorption. Bone density of the distal radius significantly increased during TTS 50 (P less than 0.02), reaching its maximum value after 6 months of therapy. Thereafter bone density declined, but more slowly than in untreated women. Our data suggest that TTS 50 has marked neuroendocrine effects, that it diminishes the incidence of hot flushes and reduces bone demineralization. By contrast, it has a very little, if any, metabolic impact on the liver or on glucose and lipid metabolism.

Administration, Cutaneous↗
PubMed1989

Effects of the antidopaminergic drug veralipride on LH and PRL secretion in postmenopausal women.

Patterns of LH and PRL secretion have been evaluated in 15 postmenopausal women before and after the chronic blockage of the D2 dopamine receptors with veralipride (100 mg twice daily, for 30 days). In addition, the possible influence of the antidopaminergic drug on the activity of the endogenous opioid system has been evaluated by the infusion of the opioid antagonist naloxone, performed before and during veralipride administration. Mean plasma LH levels were significantly blunted (p less than 0.05) and mean plasma PRL levels were significantly increased (p less than 0.001) by veralipride administration. The frequency of both LH and PRL secretory pulses was not modified, while the mean pulse amplitude of both hormones was significantly increased (p less than 0.05 for LH; p less than 0.001 for PRL) by veralipride administration. In untreated postmenopausal women naloxone infusion did not modify LH secretion. Following veralipride, the infusion of naloxone significantly increased (p less than 0.05) the mean plasma LH levels, had no influence on the frequency and significantly reduced (p less than 0.01) the amplitude of LH pulses, expressed as the percent increase from the nadir to the peak. Both before and after veralipride administration, naloxone failed to modify the pattern of PRL secretion. In untreated postmenopausal women, the percentage of concomitant PRL and LH pulses was significantly higher (p less than 0.001) during naloxone than during saline infusion, and this effect was amplified by veralipride administration (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Dopamine Antagonists↗